Basic ethers of aryl-quinolines



a Patented May 24, 1932 mam srenons 'rormM OF SWITZERLAND 1 I 'lhe relates to new basic ethers of" aryl-quinolines useful in therapeutics.

hol ona halogen-aryl-quin'oline or a substitution product thereof; or an amine on a 7 ether of an] aromatic compoundlby ring 010- snre into a basic ether of an aryhqninoline, As the r ng closurereaction there may be cited a's'an'examplejthe transformation of a basic 'ether o f an aromati amine by means of an; aldehyde" and pyroracemlc means of benzoyl cetone; W

"*Th new 1:) ses formtic agents.

'f The following examples illustrate "the invention, the 'part's 'being byw'eight i- E m'pzerj g A mixtureof 1 part of 2- phenyl-7-hydroxyquinoline, 1.5 part of chlorethyldiethylamine hydrochloride, 3 parts of potassium carbonate and parts (if-acetone is'iboiled for several hoursw After filtrationthe acetone is monohydrochloride white crystals of melting.

distilled from the filtrate and the residue} is taken up with ether. The ethereal solution is'shaken with dilute caustic alkali solution and apo a ed t ry s T 2-Ph y -i diethylammoethogyquinoline remains inthe form of a yellow oil. It is sparingly soluble in water butpfreely fsoluble in organic solve'ntsias well asin acidsl- Its-dihydrochloride forms a bright yellow crystalline powder of 'melting point 230-231? C: and its point 155-157 C,,"both soluble in water.

The same base be obtainedby the action of 2rphenyl Lbromethginyfquinoline [on diethylamine at a raised temperature. yThe 2- y v y 4 a point 112-113 0; The new compounds are obtainedby cans-3 ing ,to react; preferably in presence jof'an agent that binds acid, an amino-alkylatingo agent on anhydroxy-aryl-quinoline or a substitution product thereof; or; an "amino-211C0 ac y c I 1 h acids'saltssoluble in water. Beoause'of their high antipy V retic aCtiOn'th i r pe i sooI'ETY OF NGHEMIGAL V innus'rmr VIN BASIPE, on B 1,

BA G ETEE S OB ARYL QUiNOLIn s J "i m,JJ'r 'wi Application filed m i o, 1930, Serial NB. 451,505, a a se en;-1ey"16;119z

quinoline in p 'e sr l ce alkali; itgforms a yellowish crystalline --xpowder of; n

10f 'diethylaininoI -ethanol @61 theunse 1's;

heated for some time ifiifan oil b'ath with 8" ing jpoint 54%55 (3.; obtainable from "3 7 parts of 2-chloro 3-phenyl-quinoline (melt? 60 phosphorous "oxychloride) The massis' ex;

tract'ed'with ether and the so'diuin chloride which has been formed is separatedby .filtra tionand the solventis distilled from trate together with vthe excess of'diethylam ino-etlianol, There remains the 2-diethylani; 'ino-ethoXy-3-phenyl-quinoline in i the form Of'a bright yellow oil; freelyisoluble in organic solvents and inacids but sparingly sol- 2225 parts of '2 (para-hydroxyebhenyl)a; I qu1noline,;2.4 parts of chlorethyldiethyl-am- Its monohydrochlori'de,melts I I i ine-hydr chloride andi part o'f sodium hy-. 2' droxide are stirred together inaqneous soletion foriseveral hours 'at' aslightlyiiraised temperature. The base which separates ifsi :5

dissolved in ether and the solution is washed with Water. After distilling the ether there remains the 2-(para-diethylaminoethoXyphenyl) -qui'noline inthe form of 'a--'ne'arly ter but very freely inorganic solventsfand' 2 parts of para;piperidyl ethoxyaniliiie colorless oilwhich dissolves sparingly inwia- A 1 in acidsg Its monohydrochloride is 1 a colr; less crystallinepowder offmeltingpoi tigogl hydrochloride (obtainable by saponifylngl' the .piperidylethylether of para -acet aminophenol) 1 part of benzaldehyde'and30 parts of alcoholare heated together to boiling; In- 1 V v 1 to the boiling solution is introduced, "clropfby i 1 (1mm solution ofjl' 'partofpyroracemicacid V in lQpai'ts'ofalcohohthe wholeis-thenboiledg. 106

and water is added 'to the residue," There s 2- 3 n- ,1T63-diethylaminoethox yquinolinei 3 3. 8 Colorless melting point then separates the sparingly soluble hydrochloride 1 of "'2-phenyl-6-piperidy1-ethoxy4- -quinolinecarboxylic acid, containing Water,

in the form of smaHcana-ry elloW needles.

By heating these in a Vecuumthe Water of crystallization is lost and the bodybecomes colorless. In'or-der to obtain the free amino.-

acid the hydrochloride is dissolved inwater 3 3 3 and the solntion is neutralized cautiously with alkelisolution: The. acid which sepae rates forrns colorless crystalsand melts when 'ojfffelcohol and soliitionis heated for severalhours '8' parts of '2-phenyl-7-hy-f; droxy -quinoline I and-i7; parts'3 of d-diethyl 5 emin'o- -ehlorogpentane (colorless oil of boiling points68"69 :.C at 5 pressiire thefhydrochloride of this base,;. of melting point' 0 332 5 m y be q a isby a i "thionylchloride"to; react' c l-ethyl 8-div ethyldminopropyl-alcohol) After filtration 3 .1 i the,'ailcohollis .distilledfromthe filtrate, ind; 3

he I ethereal solution is evaporated. '3 The 2- p e y -i-(Q hy -.7-d y min rr py hyr droxy) -qninoline3of the formula j i3 f l the ,fresidi'ie is; taken up. with ether.

' remains as' a' yellow, Viscous oil of boiling r L f3'iBright yellow oil; melting pointof the 3 I White. monohydrochloride.8990 C. and. of

'point 217-218 3 G; at 0,1 mm. pressure.

In similar manner the following com-3 pounds' canbemadea -56 dihydrochloride 3 2-; he yi-7-d1-3 j tyiamiilq iyquinb theyellowish dihydrochloride 1333-1343 0.3

Y Y -P yl f7j-hdiethylilminoethox quinajlLfl 3 a Colorless 311; 33130133383;313333 3031033;3 me s33 t2 or 5 i'C-i 33 3. I "A -phenyl- Z 'd icyclohexylamino -".'eth oxy-3i quinaldine.

1053 0. 3 3 I 3 'Its colorless 'dihydrochlori'de-decomposes ---3Ye113wi$h 011ortdning oinieosgmos i 'WhQIQlIlR representse a1 lene cha n on? at l mm plressure. v V, 3 The" 2: lrdichloro 3=phenyilquinoline3 necesy 'f 'm in i l s am dgwmpd nd' is ohteineble boiling T2 'zfl -dihydroxy-3- It is sparingly soluble in Water and freely" -qninol-ines of tertiary an1ine;--and {-A a 'phenylqgroup, andf "P d f ith acids-neutral; salts-an are useful in therapeutics; I1

(diethylaminoethoxy) 3 3 fl;

' ng; at j leas ltwqica hii a oms f nd v wherein R represents an" alkylenerediozil icontaining .'a t.3 ..1ea'st .twofcarbon' atoms; X a

tertiary famine; and n the numbers l or 2,.-

and whereinone of the carbon atoms a, 0rd

I is linked With phenyl, and the group 033K 80 is? linkedwith-oneorttwos of :the. not: yet sub- 3 3 stitnted-.carbon; atoms La and- C', vQ1 With one f of the carbon atomse and'f, I -With the; 'phenyl; group; "which ii products lforl'n with,

pentics; 2; As new ,acids neutral's'sltsiand 'are useful'in thiefalf the general formula 3 wherein *R represents an a1k 1en 13di31 con-'- V 7 mining at: 1 @331 Car on toms and: al .2 tertiary aming 1 and wherein one-of the b3 i f bonratoms g b orj,c3, f'li k i and the groupfOiRiX i'sflmked 3 the not yetgsu bstitiitedf jcarbq com a; o c, oriw' th h bbi eibms 31. 0

wit theph nyl s upr ichp odupts or with acidsneutr'al salts and: are. usefuin -f erep t cs i 3 3. As. 23 511313 63 2 1 ;Q 5 V phenyl-quinolines. Ofithe. general formula wherein R represents'en alkylene chain con-1 7 talning at least 'tvqofioarbon latoms,"-X aj 1 phenyl-quinoline phosphorns oxj -chloproduct's-hastens 0f i ep i wherein the-group 0513 ;is' lin d with :o e 3 which products form with acids neutral salts and are useful in therapeutics.

5. As new products basic ethers of 2- phenyl-quinolines of the general formula V Know-can Y R representing an alkylene chain containing A at least two carbon atoms, and X a tertlary amine, which products form with aclds neuv tral salts and are useful in therapeutics.

6. As new products basic ethers of 2- phenyl-quinolines of the general formula N.R.0 CH R) V O N a E R and R meaning monovalent alkyl groups and R an alkylene chain containing at least two carbon atoms, which products form with acids neutral salts and are useful in therapeutics. p p

7. As new products basic ethers of 2- phenyl-quinolinesof the general formula and forming a white-monohydrochloride of N1t 0 o H i 5 0211/ p N a R meaning an alkylene' chain containing at least two carbon atoms, which products form with acids. neutral salts and are useful in therapeutics.

8. As a new product 2-phenyl 7-diethylaminoethoxy quinoline of the formula water, but freely soluble in organic solvents,

which is a yellow oil, sparingly soluble'in -g 

